Notch activation suppresses endothelial cell migration and sprouting via miR-223-3p targeting Fbxw7.
In Vitro Cell Dev Biol Anim
; 58(2): 124-135, 2022 Feb.
Article
en En
| MEDLINE
| ID: mdl-35194762
ABSTRACT
Angiogenesis involves temporo-spatially coordinated endothelial cell (EC) proliferation, differentiation, migration, and sprouting. Notch signaling is essential in regulating EC behaviors during angiogenesis, but its downstream mechanisms remain incompletely defined. In the current study, we show that miR-223-3p is a downstream molecule of Notch signaling and mediates the role of Notch signaling in regulating EC migration and sprouting. In human umbilical vein endothelial cells (HUVECs), Notch activation by immobilized Dll4, a Notch ligand, upregulated miR-223-3p, and Notch activation-mediated miR-223-3p upregulation could be blocked by a γ-secretase inhibitor (DAPT). miR-223-3p overexpression apparently repressed HUVEC migration, leading to attenuated lumen formation and sprouting capacities. Transcriptome comparison and subsequent qRT-PCR validation further indicated that miR-223-3p downregulated the expression of multiple genes involved in EC migration, axon guidance, extracellular matrix remodeling, and angiogenesis. In addition, miR-223-3p antagonist transfection abolished Notch-mediated repression of EC migration and sprouting. By quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and reporter assay analysis, we confirmed that miR-223-3p directly targeted F-box and WD repeat domain-containing 7 (Fbxw7). Meanwhile, Fbxw7 overexpression could efficiently rescue the impaired migration capacity of ECs under miR-223-3p overexpression. In summary, these results identify that Notch activation-induced miR-223-3p suppresses EC migration and sprouting via Fbxw7.
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Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Receptores Notch
/
Proteína 7 que Contiene Repeticiones F-Box-WD
Límite:
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article